The American Association for Cancer Research (AACR) announced today that in partnership with the Lung Cancer Initiative at Johnson & Johnson, it will fund a major grant led by University of Colorado Cancer Center investigators to pinpoint the lung tissue characteristics that allow cancer cells to grow, potentially leading to new strategies to prevent and treat the disease.

This team project will be led by James
DeGregori, PhD, CU Cancer Center Deputy Director and professor in the CU School
of Medicine Department of Biochemistry and Molecular Genetics, whose research
explores the development of cancer through the lens of evolution, as
populations of cells compete for limited resources within the ecosystem of the
body. DeGregori’s model, called Adaptive
Oncogenesis, shows that it is not necessarily mutations alone
that cause cancer, but cancer-causing mutations in cooperation with changes in
the tissue ecosystem such as inflammation, aging, and immune system imbalance
that make cells with these mutations “more fit” than other cells within the
same tissue environment.

The group includes additional Colorado
researchers from National Jewish Health and the Rocky Mountain Regional
Veterans Affairs Medical Center. Co-principal investigator, Dr. Tullia Bruno,
who trained in Colorado, will lead a collaborating team at the University of
Pittsburgh with co-investigator and pulmonologist, Dr. David Wilson.

Previous work from grant co-investigators including
Drs. York Miller, Robert Keith, Moumita Ghosh, and Dan Merrick has shown that
interventions modulating lung conditions can reduce the risk of malignant cell growth.
Together with more basic studies from DeGregori’s group, findings suggest that altered
lung environments (such as due to smoking) can offer an evolutionary advantage
to lung cancer cells, and that dampening these lung alterations can reduce this
risk.

“Think of the body like a neighborhood. If you walk into a
neighborhood with abandoned buildings and broken windows, you can guess the odds
that you’ll be mugged without necessarily having to see the mugger. That’s what
we’re doing in the lung – it’s the neighborhood that allows these shady
characters to be there,” DeGregori says.

With AACR support, the team hopes to identify the lung equivalents
of “abandoned buildings” and “broken windows” that allow them to predict cancer
risk based on conditions of the lung. Eventually, the group hopes their work
will lead to interventions to change these
conditions for the purpose of preventing or treating lung cancer.

The current study will use bronchoscopy samples from patients evaluated
for possibly cancerous nodules.

“They have nodules,” DeGregori says. “A little more than half the
time it’s nothing and a little less than half the time it’s cancer. Our goal is
to see if we can predict which is which based on other features of the lung.”

For example, it may be that bronchoscopy specimens taken from
lungs with higher levels of inflammation (as often seen in smokers) are more
likely to harbor a cancer. Previous work also hints that the balance of two types
of immune cells – cytotoxic T cells that activate the immune system, and regulatory
T cells that turn it off – may influence whether cells with cancer-causing
mutations are able to flourish.

“To use another analogy, it’s like the classic idea of seed and
soil. A malignant cell is the seed. We’re looking for features of a fertile
soil for cancer. And then we will be able to ask, how do we change that soil to make it less fertile for cancer growth?” DeGregori
says.

The work also highlights a shifting paradigm in cancer research
that prioritizes collaboration across disciplines and institutions.

“Clinician-scientists on the team will obtain the bronchoscopy
specimens; a pathologist will evaluate them; immunologists will explore immune features
of these tissues; and bioinformaticians will help us quantify what it all
means,” DeGregori says. “None of this would work without the other components.
Without any one of these pieces, the study would never get off the ground.”

The three-year, $1.5M grant is expected to accrue approximately 90
patients for evaluation. The group hopes this work will lead to additional
exploration by its members and others into the tissue conditions that support
and suppress the growth of lung and other cancers.